Epinephrine inhibits endotoxin-induced IL-1β production: roles of tumor necrosis factor-α and IL-10

1997 ◽  
Vol 273 (6) ◽  
pp. R1885-R1890 ◽  
Author(s):  
Tom Van Der Poll ◽  
Stephen F. Lowry
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Ex Vivo ◽  
Systemic Infection ◽  
Tnf Α ◽  
Cytokine Tumor Necrosis Factor ◽  
Dose Dependent Decrease ◽  
Factor Α ◽  
Necrosis Factor

Epinephrine has been found to inhibit the production of the proinflammatory cytokine tumor necrosis factor (TNF)-α and to enhance the production of anti-inflammatory cytokine interleukin (IL)-10. To determine the effect of epinephrine on IL-1β production, the following experiments were performed: 1) blood obtained from subjects at 4–21 h after the start of a continuous infusion of epinephrine (30 ng ⋅ kg−1⋅ min−1) produced less IL-1β after ex vivo stimulation with lipopolysaccharide (LPS), compared with blood drawn from subjects infused with saline; 2) in whole blood in vitro, epinephrine caused a dose-dependent decrease in LPS-induced IL-1β production, which was likely mediated via adrenergic receptors; and 3) inhibition of TNF and enhancement of IL-10 both contributed to epinephrine-induced inhibition of IL-1β production. Epinephrine, either endogenously produced or administered as a component of sepsis treatment, may attenuate excessive activity of proinflammatory cytokines early in the course of systemic infection.

scholarly journals Ectopic HOXB4 overcomes the inhibitory effect of tumor necrosis factor-α on Fanconi anemia hematopoietic stem and progenitor cells

Blood ◽  
2009 ◽  
Vol 113 (21) ◽  
pp. 5111-5120 ◽  
Author(s):  
Michael D. Milsom ◽  
Bernhard Schiedlmeier ◽  
Jeff Bailey ◽  
Mi-Ok Kim ◽  
Dandan Li ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Fanconi Anemia ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Ectopic Expression ◽  
Hematopoietic Stem ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

AbstractEctopic delivery of HOXB4 elicits the expansion of engrafting hematopoietic stem cells (HSCs). We hypothesized that inhibition of tumor necrosis factor-α (TNF-α) signaling may be central to the self-renewal signature of HOXB4. Because HSCs derived from Fanconi anemia (FA) knockout mice are hypersensitive to TNF-α, we studied Fancc−/− HSCs to determine the physiologic effects of HOXB4 on TNF-α sensitivity and the relationship of these effects to the engraftment defect of FA HSCs. Overexpression of HOXB4 reversed the in vitro hypersensitivity to TNF-α of Fancc−/− HSCs and progenitors (P) and partially rescued the engraftment defect of these cells. Coexpression of HOXB4 and the correcting FA-C protein resulted in full correction compared with wild-type (WT) HSCs. Ectopic expression of HOXB4 resulted in a reduction in both apoptosis and reactive oxygen species in Fancc−/− but not WT HSC/P. HOXB4 overexpression was also associated with a significant reduction in surface expression of TNF-α receptors on Fancc−/− HSC/P. Finally, enhanced engraftment was seen even when HOXB4 was expressed in a time-limited fashion during in vivo reconstitution. Thus, the HOXB4 engraftment signature may be related to its effects on TNF-α signaling, and this pathway may be a molecular target for timed pharmacologic manipulation of HSC during reconstitution.

scholarly journals Dexamethasone Restores the Repressive Effect of Tumor Necrosis Factor-α on Follicular Growth and E2 Secretion During the In Vitro Culture of Preantral Follicles

2021 ◽  
Author(s):  
Que Wu ◽  
Tingwei Zhuang ◽  
Zhiling Li
Keyword(s):  
Tumor Necrosis Factor ◽  
In Vitro Culture ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Follicular Growth ◽  
Tnf Α ◽  
Repressive Effect ◽  
Factor Α ◽  
Necrosis Factor

AbstractAs a proinflammatory cytokine, tumor necrosis factor-α (TNF-α) is central to the female reproductive tract and affects various phases of follicular development and uterine cycles. High levels of TNF-α play a vital role in the pathogenesis of polycystic ovary syndrome (PCOS) in patients. Clinicians know that dexamethasone can inhibit the induction of androgen by suppressing the adrenal glands which improves the status of the endocrine system in PCOS patients. We hypothesize that dexamethasone has much more functionality and can exert a therapeutic effect by antagonizing TNF-α. We added TNF-α to the follicular culture medium to simulate the high TNF-α levels observed in the endocrine environment of PCOS patients. Dexamethasone was added to the medium to determine if it could counteract the inhibitory effect of TNF-α on follicular growth and 17β-estradiol (E2) secretion. Follicular diameter, E2 concentration, follicle survival, antral-like cavity formation, and ovulation were measured to assess the effects of dexamethasone. In our work, TNF-α inhibited in vitro follicular growth and E2 secretion in a dose-dependent manner. Based on the results of the present research, we concluded that the addition of dexamethasone partially counteracts the repressive effect of TNF-α on follicle growth and E2 secretion during in vitro culture of the preantral follicles of mice. Thus, the findings in this paper suggest that dexamethasone may act as a therapy by counteracting the effects of TNF-α in PCOS patients. These results provide a new foundation for exploring the treatment of PCOS patients with dexamethasone.

The Regulation of Platelet Aggregation In Vitro by Interleukin-1 β and Tumor Necrosis Factor-α: Changes in Pregnancy and in Pre-eclampsia

1997 ◽  
Vol 78 (04) ◽  
pp. 1255-1261 ◽  
Author(s):  
J Bar ◽  
A Zosmer ◽  
M Hod ◽  
M G Elder ◽  
M H F Sullivan
Keyword(s):  
Platelet Aggregation ◽  
Tumor Necrosis Factor ◽  
Pregnant Women ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Tnf Α ◽  
Factor Α ◽  
Aggregation Of Platelets ◽  
Necrosis Factor

SummaryPlatelet activation occurs in early pregnancy in women at risk of developing pre-eclampsia. Cytokines have been implicated in the pathogenesis of pre-eclampsia, so we determined the effects of interleukin- 1β (IL-1β) and tumor necrosis factor-α (TNF-α) on the in vitro aggregation of human platelets. IL-1β increased aggregation of platelets from non-pregnant and pre-eclamptic women, and inhibited the aggregation of platelets from normal pregnant women. This latter effect was linked to a diminished P-selectin expression on ADP-stimulated whole blood platelets in normal pregnant women (p = 0.011). Platelet aggregation in response to ADP was found to be inhibited after preincubation with TNF-α in non-pregnant (38%, p = 0.01) and in normal pregnant women (54%, p = 0.001) and not affected in pre-eclamptic women. The inhibitory effects of TNF-α were mediated through the P75 receptor for TNF-α.

scholarly journals Polymorphisms of the tumor necrosis factor-α gene promoter predict for outcome after thalidomide therapy in relapsed and refractory multiple myeloma

Blood ◽  
2002 ◽  
Vol 100 (6) ◽  
pp. 2263-2265 ◽  
Author(s):  
Kai Neben ◽  
Joannis Mytilineos ◽  
Thomas M. Moehler ◽  
Astrid Preiss ◽  
Alwin Kraemer ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Gene Promoter ◽  
Nucleotide Polymorphisms ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Abstract Thalidomide (Thal) is a drug with antiangiogenic, anti-inflammatory, and immunomodulatory properties that was found to inhibit the production of tumor necrosis factor-α (TNF-α) in vitro. We studied single nucleotide polymorphisms at positions −308 and −238 of the TNF-α gene promoter and measured the corresponding TNF-α cytokine levels in 81 patients (pts) with refractory and relapsed multiple myeloma (MM) who were treated with Thal. In myeloma pts carrying the TNF-238A allele (n = 8), we found a correlation with higher pretreatment TNF-α levels in peripheral blood (P = .047). After Thal administration, this TNF-238A group had a prolonged 12-month progression-free and overall survival of 86% and 100% versus 44% and 84% (P = .003 andP = .07) in pts with the TNF-238G allele, respectively. These findings suggest that regulatory polymorphisms of the TNF-α gene can affect TNF-α production and predict the outcome after Thal therapy, particularly in those MM pts who are genetically defined as “high producers” of TNF-α.

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